title: Energy landscape, structure and rate effects on strength properties of alpha-helical proteins.
abstract: The strength of protein domains is crucial to identify the mechanical role of protein domains in biological processes such as mechanotransduction, tissue mechanics and tissue remodeling. Whereas the concept of strength has been widely investigated for engineered materials, the strength of fundamental protein material building blocks and how it depends on structural parameters such as the chemical bonding, the protein filament length and the timescale of observation or deformation velocity remains poorly understood. Here we report a systematic analysis of the influence of key parameters that define the energy landscape of the strength properties of alpha-helical protein domains, including energy barriers, unfolding and refolding distances, the locations of folded and unfolded states, as well as variations of the length and pulling velocity of alpha-helical protein filaments. The analysis is facilitated by the development of a double-well mesoscale potential formulation, utilized here to carry out a systematic numerical analysis of the behavior of alpha-helices. We compare the results against widely used protein strength models based on the Bell model, one of the simplest models used to characterize the strength of protein filaments. We find that, whereas Bell-type models are a reasonable approximation to describe the rupture of alpha-helical protein domains for a certain range of pulling speeds and values of energy barriers, the model ceases to hold for very large energy barriers and for very small pulling speeds, in agreement with earlier findings. We conclude with an application of our mesoscale model to investigate the effect of the length of alpha-helices on their mechanical strength. We find a weakening effect as the length of alpha-helical proteins increases, followed by an asymptotic regime in which the strength remains constant. We compare strand lengths found in biological proteins with the scaling law of strength versus alpha-helix filament length. The mesoscale model reported here is generally applicable to other protein filaments that feature a serial array of domains that unfold under applied strain, where a similar length-dependent strength could be observed.
authors.affiliation: Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 1-235A&B, Cambridge, MA 02139, USA.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Bertaud
authors.forename: Joshua
authors.initials: J
authors.lastname: Hester
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Jimenez
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Buehler
mesh_terms: D000465:Algorithms; D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D008422:Materials Testing; D008956:Models, Chemical; D015233:Models, Statistical; D008962:Models, Theoretical; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods
chemical_list: D011506:Proteins